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Journal of Antimicrobial Chemotherapy (2000) 46, 249-253
© 2000 The British Society for Antimicrobial Chemotherapy

Grepafloxacin against penicillin-resistant pneumococci in the rabbit meningitis model

Cynthia M. Gerbera, Luis Tovarb, Marianne Cottagnouda, Klaus A. Neftelb, Martin G. Täuberc and Philippe Cottagnoudb,*

a Department of Internal Medicine, Zieglerspital, Berne, b Department of Internal Medicine, Inselspital, Freiburgstrasse, 3010 Berne and c Institute for Medical Microbiology, University of Berne, Berne, Switzerland

Grepafloxacin, a new fluoroquinolone, produced bactericidal activity comparable to that of vancomycin and ceftriaxone in the treatment in rabbits of meningitis caused by a pneumococcal strain highly resistant to penicillin (MIC 4 mg/L) ({triangleup}log10 cfu/mL•h for grepafloxacin, -0.32 ± 0.15; dose, 15 mg/kg iv; {triangleup}log10 cfu/mL•h for vancomycin, -0.39 ± 0.18; dose, 2 x 20 mg/kg iv; {triangleup}log10 cfu/mL•h for ceftriaxone, -0.32 ± 0.12; dose, 125 mg/kg iv). Higher doses of grepafloxacin (30 mg/kg and 2 x 50 mg/kg) did not improve the killing rates. The combination of grepafloxacin with vancomycin was not significantly superior to monotherapies (P > 0.05). In vitro, grepafloxacin was bactericidal at concentrations above the MIC. Using concentrations around the MIC, addition of vancomycin to grepafloxacin showed synergic activity.

* Corresponding author. Tel: +41-316322111; Fax: +41-316323847; E-mail: pcottagn{at}insel.ch


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